Description of Research Expertise

Description of Research
Our research addresses the molecular basis of normal and neoplastic growth in the developing nervous system. We hope that by understanding the normal processes that govern formation of the brain we will uncover new approaches for the treatment of rare but very devastating pediatric brain tumors. Research in the laboratory combines basic approaches with genomics and translational science in a broad-based effort. Our experimental strategies include mouse disease models, cell culture, genomics, human tumor samples, imaging and a range of molecular techniques.

Previously, we identified the reelin gene (Reln) whose protein product is a large extracellular protein that controls cell migration and is secreted by several early populations of neurons in the developing brain. We are now examining the molecular events downstream of Reln that mediate its function. To accomplish this we are developing several conditional mutant mouse lines and we are utilizing cell and molecular biology approaches.

We are taking genomic approaches to identify molecular changes and potential drug targets for several brain tumors including medulloblastoma, atypical teratoid/rhabdoid tumors and choroid plexus carcinomas. We developed a model system with a 100 percent incidence of spontaneous medulloblastoma for use in translational studies. Recently, we found that a small molecule inhibitor of the sonic hedgehog (Shh) pathway eliminated even large tumor masses in vivo. We are continuing to analyze the mechanism of action of several anticancer drugs in tumor cells and cancer models.

Rotation Projects
Opportunities are available to investigate the response of brain tumors to molecular targeted therapies in genetic mouse models. Opportunities are also available to investigate the molecular control of cell migration in the developing brain and signaling components of the Reelin pathway. Please contact Dr. Curran for available projects.